Journal Article > ResearchFull Text
medRxiv. 2019 August 17; DOI:10.1101/19003434
Funk S, Takahashi S, Hellewell J, Gadroen K, Carrion Martin AI, et al.
medRxiv. 2019 August 17; DOI:10.1101/19003434
The Katanga region in the Democratic Republic of Congo (DRC) has been struck by repeated epidemics of measles, with large outbreaks occurring in 2010–13 and 2015. In many of the affected health zones, reactive mass vaccination campaigns were conducted in response to the outbreaks. Here, we attempted to determine how effective the vaccination campaigns in 2015 were in curtailing the ongoing outbreak. We further sought to establish whether the risk of large measles outbreaks in different health zones could have been determined in advance to help prioritise areas for vaccination campaign and speed up the response. In doing so, we first attempted to identify factors that could have been used in 2015 to predict in which health zones the greatest outbreaks would occur. Administrative vaccination coverage was not a good predictor of the size of outbreaks in different health zones. Vaccination coverage derived from surveys, on the other hand, appeared to give more reliable estimates of health zones of low vaccination coverage and, consequently, large outbreaks. On a coarser geographical scale, the provinces most affected in 2015 could be predicted from the outbreak sizes in 2010–13. This, combined with the fact that the vast majority of reported cases were in under-5 year olds, would suggest that there are systematic issues of undervaccination. If this was to continue, outbreaks would be expected to continue to occur in the affected health zones at regular intervals, mostly concentrated in under-5 year olds. We further used a model of measles transmission to estimate the impact of the vaccination campaigns, by first fitting a model to the data including the campaigns and then re-running this without vaccination. We estimated the reactive campaigns to have reduced the size of the overall outbreak by approximately 21,000 (IQR: 16,000–27,000; 95% CI: 8300–38,000) cases. There was considerable heterogeneity in the impact of campaigns, with campaigns started earlier after the start of an outbreak being more impactful. Taken together, these findings suggest that while a strong routine vaccination regime remains the most effective means of measles control, it might be possible to improve the effectiveness of reactive campaigns by considering predictive factors to trigger a more targeted vaccination response.
Journal Article > ResearchFull Text
PLOS One. 2015 July 10; Volume 10 (Issue 7); e0132422.; DOI:10.1371/journal.pone.0132422
Shanks L, Ritmeijer KKD, Piriou E, Siddiqui MR, Kliescikova J, et al.
PLOS One. 2015 July 10; Volume 10 (Issue 7); e0132422.; DOI:10.1371/journal.pone.0132422
Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.
Journal Article > ResearchFull Text
Clin Infect Dis. 2022 October 15; Volume 75 (Issue 8); 1307-1314.; DOI:10.1093/cid/ciac176
Huerga H, Khan UT, Bastard M, Mitnick CD, Lachenal N, et al.
Clin Infect Dis. 2022 October 15; Volume 75 (Issue 8); 1307-1314.; DOI:10.1093/cid/ciac176
BACKGROUND
Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet, this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs.
METHODS
We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented.
RESULTS
Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died and 7.2% experienced treatment failure.
CONCLUSIONS
Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.
Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet, this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs.
METHODS
We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented.
RESULTS
Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died and 7.2% experienced treatment failure.
CONCLUSIONS
Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.
Protocol > Research Study
Siddiqui MR, Cramond V, Goldberg J, Guzek J
2018 July 1
2. OBJECTIVES
2.1. PRIMARY OBJECTIVES
To estimate the scale of the emergency through measurement of crude mortality rate for the total population and for children under five years of age
2.2. SECONDARY OBJECTIVES
To estimate the size of the population in Palorinya settlement camp
To describe the population in terms of age, sex and household composition;
To determine the coverage of measles, polio, MenAfriVac, DPT-Hib-HepB (Pentavalent) and pneumococcal virus (PCV) vaccination in 6-59 month olds;
To determine the rate of severe and global acute malnutrition in 6-59 month olds;
To identify the most prevalent morbidities in the population in the two weeks preceding the survey;
To describe the health seeking behaviour in terms of access to primary and secondary care;
To estimate crude mortality rate for the total population and for children under five years of age before and after the SPLA advance into Equatoria, South Sudan;
To identify major causes of death, by age group and sex;
To gain knowledge of violence-related events
To determine the coverage of Long-Lasting Insecticide Treated bedNets (LLITNs)
2.1. PRIMARY OBJECTIVES
To estimate the scale of the emergency through measurement of crude mortality rate for the total population and for children under five years of age
2.2. SECONDARY OBJECTIVES
To estimate the size of the population in Palorinya settlement camp
To describe the population in terms of age, sex and household composition;
To determine the coverage of measles, polio, MenAfriVac, DPT-Hib-HepB (Pentavalent) and pneumococcal virus (PCV) vaccination in 6-59 month olds;
To determine the rate of severe and global acute malnutrition in 6-59 month olds;
To identify the most prevalent morbidities in the population in the two weeks preceding the survey;
To describe the health seeking behaviour in terms of access to primary and secondary care;
To estimate crude mortality rate for the total population and for children under five years of age before and after the SPLA advance into Equatoria, South Sudan;
To identify major causes of death, by age group and sex;
To gain knowledge of violence-related events
To determine the coverage of Long-Lasting Insecticide Treated bedNets (LLITNs)
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2020 January 24; Volume 14 (Issue 1); e0007992.; DOI:10.1371/journal.pntd.0007992
Pekelharing JE, Gatluak F, Harrison TS, Maldonado F, Siddiqui MR, et al.
PLoS Negl Trop Dis. 2020 January 24; Volume 14 (Issue 1); e0007992.; DOI:10.1371/journal.pntd.0007992
INTRODUCTION
Visceral leishmaniasis (VL) is endemic in South Sudan, where outbreaks occur frequently. Because of changes in the immune system during pregnancy, pregnant women are considered particularly vulnerable for developing complications of VL disease, including opportunistic infections. There is limited evidence available about clinical aspects and treatment outcomes of VL in pregnancy. We describe characteristics, maternal and pregnancy outcomes from a cohort of pregnant women with VL.
METHODS
We conducted a retrospective analysis using routine programme data from a MSF health facility in Lankien, Jonglei State, South Sudan, between Oct 2014 and April 2018. Records were extracted of women diagnosed with VL while pregnant, and those symptomatic during pregnancy but diagnosed during the first two weeks postpartum. Records were matched with a random sample of non-pregnant women of reproductive age (15-45 years) with VL from the same period.
RESULTS
We included 113 women with VL in pregnancy, and 223 non-pregnant women with VL. Women with VL in pregnancy presented with more severe anaemia, were more likely to need blood transfusion (OR 9.3; 95%CI 2.5-34.2) and were more often prescribed antibiotics (OR 6.0; 95%CI 3.4-10.6), as compared to non-pregnant women with VL. Adverse pregnancy outcomes, including miscarriage and premature delivery, were reported in 20% (16/81) where VL was diagnosed in pregnancy, and 50% 13/26) where VL was diagnosed postpartum. Postpartum haemorrhage was common. Pregnant women were more likely to require extension of treatment to achieve cure (OR 10.0; 95%CI 4.8-20.9), as compared to non-pregnant women with VL. Nevertheless, overall initial cure rates were high (96.5%) and mortality was low (1.8%) in this cohort of pregnant women with VL.
CONCLUSION
This is the largest cohort in the literature of VL in pregnancy. Our data suggest that good maternal survival rates are possible in resource-limited settings, despite the high incidence of complications.
Visceral leishmaniasis (VL) is endemic in South Sudan, where outbreaks occur frequently. Because of changes in the immune system during pregnancy, pregnant women are considered particularly vulnerable for developing complications of VL disease, including opportunistic infections. There is limited evidence available about clinical aspects and treatment outcomes of VL in pregnancy. We describe characteristics, maternal and pregnancy outcomes from a cohort of pregnant women with VL.
METHODS
We conducted a retrospective analysis using routine programme data from a MSF health facility in Lankien, Jonglei State, South Sudan, between Oct 2014 and April 2018. Records were extracted of women diagnosed with VL while pregnant, and those symptomatic during pregnancy but diagnosed during the first two weeks postpartum. Records were matched with a random sample of non-pregnant women of reproductive age (15-45 years) with VL from the same period.
RESULTS
We included 113 women with VL in pregnancy, and 223 non-pregnant women with VL. Women with VL in pregnancy presented with more severe anaemia, were more likely to need blood transfusion (OR 9.3; 95%CI 2.5-34.2) and were more often prescribed antibiotics (OR 6.0; 95%CI 3.4-10.6), as compared to non-pregnant women with VL. Adverse pregnancy outcomes, including miscarriage and premature delivery, were reported in 20% (16/81) where VL was diagnosed in pregnancy, and 50% 13/26) where VL was diagnosed postpartum. Postpartum haemorrhage was common. Pregnant women were more likely to require extension of treatment to achieve cure (OR 10.0; 95%CI 4.8-20.9), as compared to non-pregnant women with VL. Nevertheless, overall initial cure rates were high (96.5%) and mortality was low (1.8%) in this cohort of pregnant women with VL.
CONCLUSION
This is the largest cohort in the literature of VL in pregnancy. Our data suggest that good maternal survival rates are possible in resource-limited settings, despite the high incidence of complications.
Journal Article > ResearchFull Text
F1000Research. 2015 February 24; Volume 4; DOI:10.12688/f1000research.6122.2
Siddiqui MR, Willis A, Bil K, Singh JA, Mukomena Sompwe E, et al.
F1000Research. 2015 February 24; Volume 4; DOI:10.12688/f1000research.6122.2
Between 2011 and 2013 the number of recorded malaria cases had more than doubled, and between 2009 and 2013 had increased almost 4-fold in MSF-OCA (Médecins sans Frontières - Operational Centre Amsterdam) programmes in the Democratic Republic of the Congo (DRC). The reasons for this rise are unclear. Incorrect intake of Artemisinin Combination Therapy (ACT) could result in failure to treat the infection and potential recurrence. An adherence study was carried out to assess whether patients were completing the full course of ACT. One hundred and eight malaria patients in Shamwana, Katanga province, DRC were visited in their households the day after ACT was supposed to be completed. They were asked a series of questions about ACT administration and the blister pack was observed (if available). Sixty seven (62.0%) patients were considered probably adherent. This did not take into account the patients that vomited or spat their pills or took them at the incorrect time of day, in which case adherence dropped to 46 (42.6%). The most common reason that patients gave for incomplete/incorrect intake was that they were vomiting or felt unwell (10 patients (24.4%), although the reasons were not recorded for 22 (53.7%) patients). This indicates that there may be poor understanding of the importance of completing the treatment or that the side effects of ACT were significant enough to over-ride the pharmacy instructions. Adherence to ACT was poor in this setting. Health education messages emphasising the need to complete ACT even if patients vomit doses, feel unwell or their health conditions improve should be promoted.
Journal Article > ResearchFull Text
Confl Health. 2019 November 14; Volume 13; 52.; DOI:10.1186/s13031-019-0236-7
Crellen T, Ssonko C, Piening T, Simaleko MM, Geiger K, et al.
Confl Health. 2019 November 14; Volume 13; 52.; DOI:10.1186/s13031-019-0236-7
BACKGROUND
Provision of antiretroviral therapy (ART) during conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 110,000 people living with HIV and 5000 AIDS-related deaths in 2018. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in a 2010 survey), and was subject to repeated attacks by armed groups on civilians during the observed period.
METHODS
Conflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determined patient-level risk factors for mortality and how the risk of mortality varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using logistic regression with terms accounting for temporal autocorrelation.
RESULTS
Patients were recruited and observed in the HIV treatment program from October 2011 to May 2017. Overall 1631 patients were enrolled and 1628 were included in the analysis giving 48,430 person-months at risk and 145 deaths. The crude mortality rate after 12 months was 0.92 (95% CI 0.90, 0.93). Our model showed that patient mortality did not increase during periods of heightened conflict; the odds ratios (OR) 95% credible interval (CrI) for i) civilian fatalities and injuries, and ii) civilian abductions on patient mortality both spanned unity. The risk of mortality for individual patients was highest in the second month after entering the cohort, and declined seven-fold over the first 12 months. Male sex was associated with a higher mortality (odds ratio 1.70 [95% CrI 1.20, 2.33]) along with the severity of opportunistic infections (OIs) at baseline (OR 2.52; 95% CrI 2.01, 3.23 for stage 2 OIs compared with stage 1).
CONCLUSIONS
Our results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient-specific risk factors. The risk of mortality and recovery of CD4 T-cell counts observed in this conflict setting are comparable to those in stable resource poor settings, suggesting that conflict should not be a barrier in access to ART.
Provision of antiretroviral therapy (ART) during conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 110,000 people living with HIV and 5000 AIDS-related deaths in 2018. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in a 2010 survey), and was subject to repeated attacks by armed groups on civilians during the observed period.
METHODS
Conflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determined patient-level risk factors for mortality and how the risk of mortality varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using logistic regression with terms accounting for temporal autocorrelation.
RESULTS
Patients were recruited and observed in the HIV treatment program from October 2011 to May 2017. Overall 1631 patients were enrolled and 1628 were included in the analysis giving 48,430 person-months at risk and 145 deaths. The crude mortality rate after 12 months was 0.92 (95% CI 0.90, 0.93). Our model showed that patient mortality did not increase during periods of heightened conflict; the odds ratios (OR) 95% credible interval (CrI) for i) civilian fatalities and injuries, and ii) civilian abductions on patient mortality both spanned unity. The risk of mortality for individual patients was highest in the second month after entering the cohort, and declined seven-fold over the first 12 months. Male sex was associated with a higher mortality (odds ratio 1.70 [95% CrI 1.20, 2.33]) along with the severity of opportunistic infections (OIs) at baseline (OR 2.52; 95% CrI 2.01, 3.23 for stage 2 OIs compared with stage 1).
CONCLUSIONS
Our results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient-specific risk factors. The risk of mortality and recovery of CD4 T-cell counts observed in this conflict setting are comparable to those in stable resource poor settings, suggesting that conflict should not be a barrier in access to ART.
Journal Article > ResearchFull Text
Virol J. 2015 May 14; Volume 12 (Issue 1); DOI:10.1186/s12985-015-0306-4
Shanks L, Siddiqui MR, Abebe A, Piriou E, Pearce N, et al.
Virol J. 2015 May 14; Volume 12 (Issue 1); DOI:10.1186/s12985-015-0306-4
Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results.
Protocol > Research Study
Pijnacker R, Siddiqui MR, Rolfes E, Liddle KF, Dada M, et al.
2018 July 1
OBJECTIVES
2.1. PRIMARY OBJECTIVES
To estimate retrospectively the crude mortality rate for the total population and for children under five years of age in the MSF catchment area
2.2. SECONDARY OBJECTIVES
To describe the population surveyed by sex and age
To measure crude mortality rate for the total population and for children under five years of age
To obtain an indication of the major causes of death, as well as the age and sex distribution of the deceased
To determine the rate of severe and global acute malnutrition in 6-59 month olds;
To identify the most prevalent morbidities in the population in the two weeks preceding the survey;
To gain knowledge of violence-related events
2.1. PRIMARY OBJECTIVES
To estimate retrospectively the crude mortality rate for the total population and for children under five years of age in the MSF catchment area
2.2. SECONDARY OBJECTIVES
To describe the population surveyed by sex and age
To measure crude mortality rate for the total population and for children under five years of age
To obtain an indication of the major causes of death, as well as the age and sex distribution of the deceased
To determine the rate of severe and global acute malnutrition in 6-59 month olds;
To identify the most prevalent morbidities in the population in the two weeks preceding the survey;
To gain knowledge of violence-related events
Protocol > Research Study
Siddiqui MR, Cramond V, Barre I, Johnson DC
2018 July 1
OBJECTIVES
2.1. PRIMARY OBJECTIVES
To estimate the scale of the emergency through measurement of crude mortality rate for the total population and for children under five years of age
2.2. SECONDARY OBJECTIVES
To estimate the size of the population in Rhino (Ofua) settlement camp
To describe the population in terms of age, sex and household composition;
To determine the coverage of measles, polio, MenAfriVac, DPT-Hib-HepB (Pentavalent) and pneumococcal virus (PCV) vaccination in 6-59 month olds;
To determine the rate of severe and global acute malnutrition in 6-59 month olds;
To identify the most prevalent morbidities in the population in the two weeks preceding the survey;
To describe the health seeking behaviour in terms of access to primary and secondary care;
To estimate crude mortality rate for the total population and for children under five years of age before and after the SPLA advance into Equatoria, South Sudan;
To identify major causes of death, by age group and sex;
To gain knowledge of violence-related events
To determine the coverage of Long-Lasting Insecticide Treated bedNets (LLITNs)
2.1. PRIMARY OBJECTIVES
To estimate the scale of the emergency through measurement of crude mortality rate for the total population and for children under five years of age
2.2. SECONDARY OBJECTIVES
To estimate the size of the population in Rhino (Ofua) settlement camp
To describe the population in terms of age, sex and household composition;
To determine the coverage of measles, polio, MenAfriVac, DPT-Hib-HepB (Pentavalent) and pneumococcal virus (PCV) vaccination in 6-59 month olds;
To determine the rate of severe and global acute malnutrition in 6-59 month olds;
To identify the most prevalent morbidities in the population in the two weeks preceding the survey;
To describe the health seeking behaviour in terms of access to primary and secondary care;
To estimate crude mortality rate for the total population and for children under five years of age before and after the SPLA advance into Equatoria, South Sudan;
To identify major causes of death, by age group and sex;
To gain knowledge of violence-related events
To determine the coverage of Long-Lasting Insecticide Treated bedNets (LLITNs)